Imidazoline BL11282 causes insulin release only when blood sugar is high
Imidazoline compound BL11282 is a small organic substance that enhances insulin release. Unlike other compounds that turn on insulin release at both low and high levels of blood sugar, BL11282 does so only when sugar concentrations are high.
Dependency on ion flow for rising insulin levels may result in hypoglycemia
Pancreatic beta cells in patients with type 2 diabetes do not produce enough insulin. To overcome the challenge, potassium channels can be closed by pharmacological substances like currently used sulfonylurea and glinide compounds. This results in opening of calcium channels and thereby stimulation of insulin release. Unfortunately, this closure of potassium channels takes place even at low glucose concentration, resulting in a too much blood sugar drop, a condition known as hypoglycemia. It heavily affects the brain’s functions and possibly results in death.
BL11282-enhanced insulin release is dependent only on glucose levels
BL11282 does not interfere with the activity of potassium channels. This imidazoline compound is a glucosensitizer, a substance that is sensitive to glucose concentrations. In combination with high levels of glucose, it fuels beta-cell capacity to release insulin to the blood.
Imidazoline BL11282 is a lead candidate for an oral glucosensitizer with no stability issues
When islets of Langerhans from diabetic animals are treated with BL11282, their insulin secreting function is fully restored. Organic compounds of this type have an advantage over peptides, such as glucagon-like peptide 1, as they are stable and can be formulated as a pill. With BL11282 as a lead compound, Biocrine works on beta-cell target evaluation and clarification of molecular mechanisms of action.
Read more about imidazolines:
- Proteins in the insulin-secreting cell line MIN6 bind the imidazoline compound BL11282. Shafqat J, Ishrat M, Jägerbrink T, Sillard R, Mäeorg U, Efendic S, Berggren PO, Zaitsev SV, Jörnvall H. FEBS Lett. 2008 May 14;582(11):1613-7
- Arachidonic acid signaling is involved in the mechanism of imidazoline-induced KATP channel-independent stimulation of insulin secretion. Sharoyko VV, Zaitseva II, Leibiger B, Efendić S, Berggren PO, Zaitsev SV. Cell Mol Life Sci. 2007 Nov;64(22):2985-93.
- Differential protein expression in pancreatic islets after treatment with an imidazoline compound. Jägerbrink T, Lexander H, Palmberg C, Shafqat J, Sharoyko V, Berggren PO, Efendic S, Zaitsev S, Jörnvall H.. Cell Mol Life Sci. 2007 May;64(10):1310-6.
- Monomeric G-protein, Rhes, is not an imidazoline-regulated protein in pancreatic beta-cells. Sharoyko VV, Zaitseva II, Varsanyi M, Portwood N, Leibiger B, Leibiger I, Berggren PO, Efendić S, Zaitsev SV. Biochem Biophys Res Commun. 2005 Dec 23;338(3):1455-9.
- Two generations of insulinotropic imidazoline compounds. Efendic S, Efanov AM, Berggren PO, Zaitsev SV. Diabetes. 2002 Dec; 51(S3):S448-S454
- The novel imidazoline compound BL11282 potentiates glucose-induced insulin secretion in pancreatic beta-cells in the absence of modulation of K(ATP) channel activity. activityEfanov AM, Zaitsev SV, Mest HJ, Raap A, Appelskog IB, Larsson O, Berggren PO, Efendic S. Diabetes. 2001 Apr;50(4):797-802.
- Imidazoline compounds protect against interleukin 1β-induced beta-cell apoptosis. . Zaitsev SV, Appelskog IB, Kapelioukh IL, Yang SN, Köhler M, Efendic S, Berggren PO. Diabetes. 2001 Feb;50(S1):S70-S76
- Imidazoline compounds stimulate insulin release by inhibition of KATP channels and interaction with the exocytotic machinery. Zaitsev SV, Efanov AM, Efanova IB, Larsson O, Ostenson CG, Gold G, Berggren PO, Efendić S. Diabetes. 1996 Nov; 45:1610-1618